ABSTRACT Support is requested for a Keystone Symposia conference entitled Mobile Genetic Elements and Genome Plasticity organized by Drs. Marlene Belfort, Evan E. Eichler, Henry L. Levin and Lynne E. Maquat. The conference will be held February 11 -15, 2018 at the Eldorado Hotel & Spa in Santa Fe, New Mexico. Transposable elements are potent sources of genetic variation that also regulate the expression of large gene networks. They constitute the majority of genomic DNA in many eukaryotes, and they dramatically shape genetic content by causing insertions, deletions, rearrangements and sequence duplications. Of increasing significance is the link of these mobile elements to diseases such as cancer and neurodegeneration. Sequencing of human populations demonstrates that active transposable elements are substantially more prevalent than previously appreciated. The aims of this conference are to: 1) Apply recent innovations in high-throughput sequencing and genome analysis to the study of transposon biology and genome dynamics; 2) Discuss the discovery of cellular systems that inhibit transposon activity as examples of the evolutionary arms race between mobile DNA and their hosts; 3) Describe active transposition during neurogenesis and in tumor cells and raise questions about the role of mobile DNA in brain development and cancer; and 4) Discern mechanistic aspects of element mobility from bacteria to humans. This symposium will foster ties between leaders in the field of transposon function and biology with the pioneers of genome analysis, a link that is still tenuous and nascent. Discussions of transposon activity and genome dynamics will focus on mechanistic models. Methods applied to these problems will include molecular structures, biochemistry, expression studies and bioinformatic analyses. The transposons and hosts represented in this meeting include diverse examples from eubacteria, archaea, protists, plants and mammals.